Uterine blood flow increases in response to estrogen, and interruption of this response leads to abnormal uterine function. Uterine vasodilation does not occur immediately after administration of estrogen, but starts after a time lag of 30-60 minutes. This observation has suggested that estrogen works through a mediator released in the 30-60 minute time lag. Our previous work and present pilot studies indicate that estrogen reduceds adrenergic vasoconstrictor tone. We also have evidence that estrogen can be hydroxylated to catecholestrogens by uterine arteries, and that inhibition of this conversion prevents estrogen-induced increases in uterine blood flow. Our earlier work indicates that prostaglandins also play a significant role in modulating uterine vascular responses to estrogen. We hypothesize that estrogen is metabolized to a catecholestrogen which, in turn, alters pervascular norepinephrine turnover so as to reduce vasoconstrictor tone. We postulate further, that prostaglandins, produced in response to estrogens, modulate this adrenergic change. We will use light, scanning and transmission microscopy to characterize the uterine artery morphology; immunohistochemistry to identify sites of estrogen binding; in vitro incubation with 3H-precursors followed by high pressure liquid chromatography to identify catecholestrogens and prostaglandins produced by the uterine artery; in vivo testing of estrogens and catecholestrogens in pigs and rats instrumented with electromagnetic or Doppler blood flow probes; pharmacologic agents to explore the mechanisms underlying the estrogen-vascular response; and immunochemical/biochemical methods to quantitate steroid hormones, uterine arterial catecholamines and adrenergic receptors.